The mechanisms leading to long-term human renal transplant function are poorly understood and form a focal point for this program project grant which applies monoclonal antibody technology diagnostically and therapeutically. The recipients of 50 cadaver transplants each year will undergo one of three immunosuppressive protocols and be followed thereafter with non-specific assays of overall immunological status as well as specific assays. We will rely on the Fluorescent Activated Cell Analyzer and Sorter (FACAS) and monoclonal antibodies to measure concentrations of T cell subsets and their turnover rates in the peripheral blood. Lymphocytes and monocytes separated by the FACAS will be examined for their state of activation by measurements of lymphokine and monokine release. An ELISA test will be developed to detect CMV in peripheral buffy coat. Donor-specific immune responses will employ MLC, CML and cytotoxic antibody tests against cryo-preserved donor spleen cells. Intensive testing will occur when ATG treatment is stopped and lymphocytes are regenerating. Data obtained in these monitoring studies will be entered into a CLINFO computer program. Two new lines of investigation will be developed. First, the nature of the hosts' response to monoclonal antibodies (OKT-3) will be scrutinized to determine the frequency and significance of anti-idiotype reactions. If antibody generated to OKT-3 has the specificity of the T cell receptor, would not the anti-idiotype response itself block the responses of T cells and extend the therapeutic benefit? Second, we will study monocyte functions as they are suppressed by our existing monoclonal antibodies reacting specifically with monocytes. We anticipate that functional assays will enable us to obtain monocyte monoclonal antibodies capable of blocking antigen processing. These new monoclonal antibodies and those distinguishing murine T cell subsets will be studied singly and in concert for their ability to promote graft acceptance in mice. Human reactive monoclonal antibodies having comparable in vitro specificities will then be selected for clinical application possibly by year 4 of the proposal.